Process for production of z-amino



Patented June 14, 1949 UNITED STATES PATENT OFFICE PROCESS FOR PRODUCTION OF Z-AMINO PYRIIWIDINES AND 2-AMINO GLYOXA LINES Wallace Frank Short and Peter Oxley, Nottingham, England, assignors to Boots Pure Drug Company Limited, Nottingham, England, a company of Great Britain No Drawing. Application June 3, 1946, Serial No. 674,032. In Great Britain June 19; 1945 8 Claims.

This invention relates to the production of salts of heterocyclic compounds containing the grouping -N=C(NH2)NH-. These salts are useful as intermediates in the preparation of, compounds of pharmacological importance.

According to the invention, salts of heterocyclic compounds containing the aforesaid grouping are obtained by reacting dicyandiamide with a mono acid salt of a diamine of the formula where HX is the acid used to form the salt and a: is an integer selected from the group consisting of 2 and 3.

The heterocyclic compounds of which the salts are formed are, therefore, represented by a ring system having the formula :1: having the significance stated. When a: is 2 the product will be 2-amino-4z5-dihydroglyoxaline and when :1: is 3 the product is a substituted tetrahydropyrimidine.

Instead of a mono acid salt of the diamine (either preformed or made in situ) the di-acid salt may be used, in which case, a guanidine salt is also formed, and this is no doubt due to the reaction between unreacted dicyandiamide and the ammonium salt formed in the ring closure.

In order that the invention may be easily understood and readily carried into effect, the following examples are given, but the invention is not limited thereto.

Example 1 In the preparation of 2-amino-4z5-dihydroglyoxaline toluene-p-sulphonate, a 'mixture of 2.1 g. of dicyandiamide and 11.6 g. of ethylenedi amine mono-toluene-p-sulphonate is heated at a temperature of 140 C. for 2% hours. During heating ammonia is evolved. After cooling the product is crystallised from alcohol whereupon Z-amino 4:5 dihydroglyoxaline toluene-p-sulphonate is obtained. in the form of crystals having a melting point of 166-16'7 0. (found N,16.6% C1uI-I15O3N3S requires N, 16.3%)

2 Example 2 In the preparation of 2-amino-4:5-dihydroglyoxaline toluene-p-sulphonate, a mixture of 8.4 g. of dicyandiamide and 40.4 g. of ethylenediamine di-toluene-p-sulphonate is heated at a temperature of 220 C. for 20 minutes. After cooling, the product is dissolved in 250 cc. of hot water. On cooling the solution guanidine toluene-p-sulphonate separates in the form of crystals and is filtered ofi. The aqueous motherliquor is evaporated to dryness and the residue is crystallised from methyl alcohol whereupon 2-amino 4:5 dihydroglyoxaline toluene-p-sulphonate separates in the form of crystals having a melting point of 166 C.

Example 3 which comprises the steps of reacting .dicyandiamide with a salt of a diamine of the formula where :c is an integer selected from the group consisting of 2 and 3 and recovering the heterocyclic compound formed by the reaction.

2. A process for the production of salts of heterocyclic compounds represented by the ring system E on 2), C.NH1

which comprises the steps of reacting dicyandiamide with a mono acid. salt of a diamine of the formula NH: (Cfli NHz and recovering the heterocyciic compound formed by the reaction, a: being an integer selected from the group consisting of 2 and 3.

3. A process for the production of saltso'fheterocyclic compounds represented by the ring system which comprises the steps of reecting fiiyeindiamide with a di-acid salt of a diamine ofth'e formuia recovering the heterocyclic compound formed ",by therea' ction, a: being an integer s'ele'cted'from "the group 'consisting'of 2*and 3.

4. A'process as claimed in claim 1;iii which the 'ecid'used to" form the salt istoluene' p-suip-iionic "acid. I A process for'the production of esaitof a.

hterocycli'c compound represented by the Ting :"'yStem "which comprises" the steps" of reacting" 'dicyan- '-dianiide" with a" salt of ethylene dimine *andre- '4 covering the heterocyclic compound formed by the reaction.

6. A process for the production of a, salt of a ---heterocyclic-;compound-represented by the ring 5 (Ca CJNHQ 6"' whicif compiisesthe steps of reacting dicyandiit'hi'ciflz'cm'prises the-steps of reacting dicyehdihmide' witn' ethyiene uiamine toiuene-'-'p-'suipho- -*nate"'and-'-'-i'ecovering the heterocyciiecompound formed;by the'i-eaction.

5 8. A process fcrtheproductionof aitoiuenemwhich comprises the steps of reacting dicyandiamide with trtmethylene diamine toluene-p-sulphonate and recovering the heterocyclic comeaund ranriea by the r ctiOn,

PETER OXLEY.

No" references cited. 

